Werner syndrome is a premature aging disorder characterized by graying and loss of hair, cataracts, short stature, skin ulcers, type-2 diabetes, myocardial infarction, atherosclerosis, and malignancy. More than half of Werner syndrome patients (55%) get diabetes. However, there is limited understanding of the mechanism involved in Werner syndrome-associated diabetes. This lack of information makes it difficult to target diabetes in WS patients. In the current project, we will be investigating the role of insulin signaling in Wrn-deficient mice, C.elegans and cell line models. We will perform analyses to determine the metabolic deregulation in Wrn-deficient model systems. The proposed investigation will provide critical insight towards understanding the molecular pathogenesis associated with type-2 diabetes in WS patients. This study is of high clinical relevance and upon successful completion we hope will provide therapeutic strategies to target diabetes in WS patients.